Abstract
This chapter focuses on brain somatostatin-related peptides. Somatostatin-14 was originally characterized as a hypothalamic neurohormone responsible for the inhibition of pituitary growth hormone secretion. In the mammalian brain, two genes encode for the prosomatostatin-derived peptides, somatostatin-14 and -28, and procortistatin-related ones, respectively. Somatotropin release inhibiting factor (SRIF) immunoreactivity is largely distributed in many neurons in mammalian brain, including the human brain. The highest levels are found in the mediobasal hypothalamus and median eminence, amygdala, preoptic area, accumbens nucleus, cerebral cortex, striatum olfactory regions, and brain stem. SRIF mediates its biological functions via at least six receptor subtypes, termed sstl, sst2A, sst2B, sst3, sst4, and sst5, which all belong to the family of seven transmembrane domain G-protein-coupled receptors. With the noticeable exception of sst4, all subtypes do internalize in various cellular models following agonist treatment. In the brain, this has only been shown in vivo for the sst2 receptor. Although the sst2 receptor is the candidate likely to mediate the anticonvulsant effects of SRIF in the rat hippocampus, in the mouse hippocampus recent observations support a central role of sst4 and/or sst1 receptors in mediating SRIF inhibition of epileptiform activity. © 2006 Elsevier Inc. All rights reserved.